The primary objectives of the proposed research are; (a) to examine the nature of (and relations between) UV and X-ray-induced lethal lesions leading to chromosomal aberrations in vertebrate cells, (b) to enhance understanding of intracellular processes, triggered by radiation, which lead to aberrations and cell death, (c) to enhance understanding of mechanisms by which cells repair or otherwise recover from such lesions. Synchronous cultures of vertebrate cells which possess the photoreactivating (PR) enzyme, and placental mammalian cells, apparently lacking the enzyme, are exposed to combinations of gamma radiation, UV light, and various metabolic inhibitors. Cells are assayed for aberration yields, reproductive death, and related repair at appropriate intervals following exposures. This approach is yielding information concerning many aspects of the radiosensitivity of vertebrate cells and changes in the structure of interphase chromosomes as cells progress through the cell cycle. Results of such studies on cellular radiosensitivity could have implications for improvements in the therapeutic uses of radiation. Any elucidation of the structure and organization of interphase chromosomes could aid in the description of fundamental genetic mechanisms of interest to those involved in numerous biomedical problems.